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However, less is known about brain functional connectivity during acute pain processing in idiopathic SFN.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>We conducted fMRI with thermal heat pain application (left volar forearm) in 32 idiopathic SFN patients and 31 healthy controls. We performed functional connectivity analyses with right supplementary motor area (SMA), left insula, and left caudate nucleus (CN) as seed regions, respectively. Since pathogenic <jats:italic>gain\u2010of\u2010function<\/jats:italic> variants in voltage gated sodium channels (Nav) have been linked to SFN pathophysiology, explorative connectivity analyses were performed in a homogenous subsample of patients carrying rare heterozygous missense variants.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>For right SMA, we found significantly higher connectivity with the right thalamus in SFN patients compared to controls. This connectivity correlated significantly with intraepidermal nerve fibre density, suggesting a link between peripheral and central pain processing. We found significantly reduced connections between right SMA and right middle frontal gyrus in patients with Nav variants. Likewise, connectivity between left CN and right frontal pole was decreased.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusions<\/jats:title><jats:p>Aberrant functional connectivity in SFN is in line with previous research on other chronic pain syndromes. Functional connectivity changes may be linked to SFN, highlighting the need to determine if they result from peripheral changes causing abnormal somatosensory processing. This understanding may be crucial for assessing their impact on painful symptoms and therapy response.<\/jats:p><\/jats:sec><jats:sec><jats:title>Significance statement<\/jats:title><jats:p>We found increased functional connectivity between SMA and thalamus during painful stimulation in patients with idiopathic SFN. Connectivity correlated significantly with intraepidermal nerve fibre density, suggesting a link between peripheral and central pain processing. Our findings emphasize the importance of investigating functional connectivity changes as a potential feature of SFN.<\/jats:p><\/jats:sec>","DOI":"10.1002\/ejp.4720","type":"journal-article","created":{"date-parts":[[2024,8,28]],"date-time":"2024-08-28T07:14:26Z","timestamp":1724829266000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Painful stimulation increases functional connectivity between supplementary motor area and thalamus in patients with small fibre neuropathy"],"prefix":"10.1002","volume":"29","author":[{"ORCID":"https:\/\/orcid.org\/0009-0001-2213-7839","authenticated-orcid":false,"given":"Sebastian","family":"Scheliga","sequence":"first","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty RWTH Aachen University  Aachen Germany"},{"name":"Scientific Center for Neuropathic Pain Aachen, SCNAachen Uniklinik RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maike F.","family":"Dohrn","sequence":"additional","affiliation":[{"name":"Scientific Center for Neuropathic Pain Aachen, SCNAachen Uniklinik RWTH Aachen University  Aachen Germany"},{"name":"Department of Neurology, Medical Faculty RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Thilo","family":"Kellermann","sequence":"additional","affiliation":[{"name":"Department of Psychiatry, Psychotherapy and Psychosomatics, Medical Faculty RWTH Aachen University  Aachen Germany"},{"name":"Scientific Center for Neuropathic Pain Aachen, SCNAachen Uniklinik RWTH Aachen University  Aachen Germany"},{"name":"Institute of Neuroscience and Medicine: JARA\u2010Institute Brain Structure Function Relationship (INM 10) Research Center J\u00fclich, Wilhelm\u2010Johnen\u2010Stra\u03b2e  J\u00fclich Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Angelika","family":"Lampert","sequence":"additional","affiliation":[{"name":"Scientific Center for Neuropathic Pain Aachen, SCNAachen Uniklinik RWTH Aachen University  Aachen Germany"},{"name":"Institute of Neurophysiology, Medical Faculty RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Roman","family":"Rolke","sequence":"additional","affiliation":[{"name":"Scientific Center for Neuropathic Pain Aachen, SCNAachen Uniklinik RWTH Aachen University  Aachen Germany"},{"name":"Department of Palliative Medicine, Medical Faculty RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Barbara","family":"Namer","sequence":"additional","affiliation":[{"name":"Scientific Center for Neuropathic Pain Aachen, SCNAachen Uniklinik RWTH Aachen University  Aachen Germany"},{"name":"Institute of Neurophysiology, Medical Faculty RWTH Aachen University  Aachen Germany"},{"name":"Research Group Neuroscience, Interdisciplinary Centre for Clinical Research, Medical Faculty RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Greta Z.","family":"Peschke","sequence":"additional","affiliation":[{"name":"Scientific Center for Neuropathic Pain Aachen, SCNAachen Uniklinik RWTH Aachen University  Aachen Germany"},{"name":"Department of Neurology, Medical Faculty RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nortje","family":"van den Braak","sequence":"additional","affiliation":[{"name":"Scientific Center for Neuropathic Pain Aachen, SCNAachen Uniklinik RWTH Aachen University  Aachen Germany"},{"name":"Department of Neurology, Medical Faculty RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Annette","family":"Lischka","sequence":"additional","affiliation":[{"name":"Scientific Center for Neuropathic Pain Aachen, SCNAachen Uniklinik RWTH Aachen University  Aachen Germany"},{"name":"Institute for Human Genetics and Genomic Medicine, Medical Faculty RWTH Aachen University  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marc","family":"Spehr","sequence":"additional","affiliation":[{"name":"Scientific Center for Neuropathic Pain Aachen, SCNAachen Uniklinik RWTH Aachen University  Aachen Germany"},{"name":"Department of Chemosensation RWTH Aachen University, Institute for Biology II  Aachen Germany"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Han\u2010Gue","family":"Jo","sequence":"additional","affiliation":[{"name":"Scientific Center for Neuropathic Pain Aachen, SCNAachen Uniklinik RWTH Aachen University  Aachen Germany"},{"name":"School of Computer Science &amp; 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